The advent of antibiotics for treating bacterial infections is considered as one of the major advances in modern medicine. However, compared with other drugs, the lifetime of antibiotics for clinical use has been substantially limited by the phenomenon of antibiotic resistance (Rossolini and Thaller 2010). Owing to the use and misuse of antimicrobials during past decades, majority of clinically important bacteria have developed multiple antibiotics resistance. Such infections are severe, difficult to manage and require longer and more complex treatments (Levy and Marshall 2004; Aiyegoro et al. 2011; Alanis 2005). In this scenario, it is imperative to develop new antimicrobials or new practices of delivery that are effective for the treatment of infectious diseases caused by drug-resistant microorganisms (Aiyegoro et al. 2011).
To overcome the problem of antibiotic resistance, the approaches such as nanotechnology, genomics are being developed (Allahverdiyev et al. 2011; Rossolini and Thaller 2010). However, these approaches require detailed study for each drug, response by the target organism and are specific in nature. Combined antibiotic therapy is an alternative approach which is being practiced against Tuberculosis for over fifty years involving the drugs with different modes of action (Englander and Friedman 2010). Based on this approach, the drug synergism between antibiotics and bioactive plant extracts has also been demonstrated (Adwan and Mhanna, 2008).
Further, biosurfactants are coming up as emerging class of biomedical compounds that are suitable alternative to synthetic medicines and antimicrobial agents, and could be used as safe and effective therapeutic agents or probiotics, especially at a time when drug resistance among causal organisms for many life-threatening diseases is on the rise (Singh and Cameotra 2004). Sophorolipid (SL) is a promising candidate for such applications being produced by non pathogenic yeasts, such as Candida bombicola, Candida apicola and Candida bogoriensis. They are generally present in the form of disaccharide sophoroses (2-O-β-D-glucopyranosyl-D-glucopyranose) linked β glycosidically to the hydroxyl group at the penultimate carbon of fatty acids (Bisht et al. 1999). These SLs possesses not only antimicrobial action but also act as antifungal, antialgal, antimycoplasma and antiviral agents (Van Bogaert et al. 2007). The proposed primary mechanism of action of these surfactants is membrane lipid order perturbation, which compromises the viability of microorganisms (Azim A et al. 2006). Moreover SLs offer the advantages of biodegradability, low ecotoxicity and the production based on renewable-resource substrates. The US FDA has also approved biosurfactants/sugar esters for the use in food and pharmaceuticals. SLs are not irritating to the skin, do not trigger allergic reactions and have an oral safety level which is greater than or equal to 5 mL/kg weight. Cytotoxicity was evaluated with human epidermal keratinocytes and was proven to be low (Van Bogaert et al. 2011).
Sun, X. et al., 2004 have demonstrated the synergistic effects of combination of SL and loess for harmful algal bloom mitigation to bring down the effective dose of both when used individually (Sun et al. 2004). MannosylErythritol Lipid-A, a type of glycolipidic biosurfactant containing cationic liposomes promoted the gene transfection efficiency five to seven times with mammalian cultured cells (Inoh et al. 2001).
Antibiotic agents are thought to diffuse freely through the cell wall of gram-positive bacteria. However, in gram-negative bacteria the diffusion of a given antibiotic agent depends on the permeability of the outer membrane. This permeability is determined by the particular structure of the membrane, which is composed of proteins and an asymmetric lipid bilayer (Gutmann et al. 1984). The outer membrane of bacteria contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. Gram-negative bacteria are responsible for a large proportion of antibiotic-resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm (Pagès et al. 2008). Thus while addressing the issue of antibiotic resistance, enhancing the permeability of drugs is of fundamental importance.
Combined antibiotic therapy has been shown to delay the emergence of bacterial resistance and also produces desirable synergistic effects in the treatment of bacterial infections (Adwan and Mhanna 2008). Also in case of nanoparticles, when they are used together with antibiotics; advantage is conferred that if bacteria have resistance against one of the components, a further component could kill them in a different manner (Rai et al. 2010).
The sophorolipid combinations with one or more known antiviral agents or one or more known spermicidal agents to produce alternative antiviral agents and spermicidal agents reported in US 20120231068 (Gross, Richard A).
In the light of the above, there is a need in the art to develop en effective antibiotic composition that can be successfully used against antibiotic resistance. Further, it is evident that none of the prior art reports a synergistic pharmaceutical composition comprising sophorolipid in combination with an antibiotic.